Lecture # 5Second class/ 2015

Acid-Base Balance

Terms

Acid Any substance that can yield a hydrogen ion

(H+) or hydronium ion when dissolved in water Release of proton or H+

Base Substance that can yield hydroxyl ions (OH-) Accept protons or H+

Terms

pK/ pKa Negative log of the ionization constant of an acid Strong acids would have a pK <3 Strong base would have a pK >9

pH Negative log of the hydrogen ion concentration pH= pK + log([base]/[acid]) Represents the hydrogen concentration

Terms

Buffer Combination of a weak acid and /or a

weak base and its salt What does it do?

Resists changes in pH

Effectiveness depends on pK of buffering system pH of environment in which it is placed

Terms

Acidosis pH less than 7.35

Alkalosis pH greater than 7.45

Note: Normal pH is 7.35-7.45

Acid-Base Balance

Function Maintains pH homeostasis Maintenance of H+ concentration

Potential Problems of Acid-Base balance Increased H+ concentration yields decreased pH Decreased H+ concentration yields increased

pH

Regulation of pH

Direct relation of the production and retention of acids andbases

Systems Respiratory Center and Lungs Kidneys Buffers

Found in all body fluids Weak acids good buffers since they can tilt a reaction

in the other direction Strong acids are poor buffers because they make the

system more acid

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Blood Buffer Systems

Why do we need them? If the acids produced in the body from the

catabolism of food and other cellularprocesses are not removed or buffered,the body’s pH would drop

Significant drops in pH interferes with cellenzyme systems.

Blood Buffer Systems

Four Major Buffer Systems Protein Buffer systems

Amino acids Hemoglobin Buffer system

Phosphate Buffer system Bicarbonate-carbonic acid Buffer system

Blood Buffer Systems

Protein Buffer System Originates from amino acids

ALBUMIN- primary protein due to highconcentration in plasma

Buffer both hydrogen ions and carbondioxide

Blood Buffering Systems

Hemoglobin Buffer System Roles Binds CO2

Binds and transports hydrogen andoxygen

Participates in the chloride shift Maintains blood pH as hemoglobin

changes from oxyhemoglobin todeoxyhemoglobin

Blood Buffer Systems

• Phosphate Buffer System• Has a major role in the elimination of H+

via the kidney• Assists in the exchange of sodium for

hydrogen• It participates in the following reaction

• HPO-24 + H+ H2PO –

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• Essential within the erythrocytes

Blood Buffer Systems

Bicarbonate/carbonic acid buffersystem Function almost instantaneously Cells that are utilizing O2, produce CO2, which

builds up. Thus, more CO2 is found in the tissuecells than in nearby blood cells. This results in apressure (pCO2).

Diffusion occurs, the CO2 leaves the tissuethrough the interstitial fluid into the capillaryblood

Bicarbonate/Carbonic Acid Buffer

Carbonicacid

Bicarbonate

Conjugatebase

Excreted inurine

Excretedby lungs

Bicarbonate/carbonic acid buffer system

How is CO2 transported? 5-8% transported in dissolved form A small amount of the CO2 combines directly

with the hemoglobin to formcarbaminohemoglobin

92-95% of CO2 will enter the RBC, and underthe following reaction CO2 + H20 H+ + HCO3

-

Once bicarbonate formed, exchanged forchloride

Henderson-Hasselbalch Equation

Relationship between pH and thebicarbonate-carbonic acid buffersystem in plasma

Allows us to calculate pH

Henderson-Hasselbalch Equation

General Equation

pH = pK + log A-

HA

Bicarbonate/Carbonic Acid system

o pH= pK + log HCO3H2CO3 ( PCO2 x 0.0301)

Henderson-Hasselbalch Equation

1. pH= pK+ log HHA

2. The pCO2 and the HCO3 are read or derived from the blood gas analyzerpCO2= 40 mmHgHCO3

-= 24 mEq/L

3. Convert the pCO2 to make the units the samepCO2= 40 mmHg * 0.03= 1.2 mEq/L

3. Lets determine the pH:4. Plug in pK of 6.1

5. Put the data in the formulapH = pK + log 24 mEq/L

1.2 mEq/LpH = pK + log 20pH= pK+ 1.30pH= 6.1+1.30pH= 7.40

The Ratio….

Normal is : 20 = Kidney = metabolic1 Lungs respiratory

The ratio of HCO3- (salt) to H2CO3 ( acid) is

normally 20:1

Allows blood pH of 7.40 The pH falls (acidosis) as bicarbonate

decreases in relation to carbonic acid The pH rises (alkalosis) as bicarbonate

increases in relation to carbonic acid

Physiologic Buffer Systems

Lungs/respiratory Quickest way to respond, takes minutes

to hours to correct pH Eliminate volatile respiratory acids such

as CO2

Doesn’t affect fixed acids like lactic acid Body pH can be adjusted by changing

rate and depth of breathing “blowing off” Provide O2 to cells and remove CO2

Physiologic Buffer Systems

Kidney/Metabolic Can eliminate large amounts of acid Can excrete base as well Can take several hours to days to correct pH Most effective regulator of pH

If kidney fails, pH balance fails

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Acid-Base Balance• Electrolytes that ionize in water and release

hydrogen ions are acids; those that combine withhydrogen ions are bases.

• Sources of Hydrogen Ions– Most hydrogen ions originate as by-products of

metabolic processes, including: the aerobic andanaerobic respiration of glucose, incomplete oxidationof fatty acids, oxidation of amino acids containingsulfur, and the breakdown of phosphoproteins andnucleic acids.

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Acid-Base Imbalances• Acidosis

– Two major types of acidosis are respiratory andmetabolic acidosis.

• Respiratory acidosis results from an increase of carbonicacid caused by respiratory center injury, air passageobstructions, or problems with gas exchange.

• Metabolic acidosis is due to either an accumulation of acidsor a loss of bases and has many causes including kidneydisease, vomiting, diarrhea, and diabetes mellitus.

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Acid-Base Imbalances– Increasing respiratory rate or the amount of hydrogen

ions released by the kidney can help compensate foracidosis.

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Acid-Base Imbalances• Alkalosis

– Alkalosis also has respiratory and metabolic causes.• Respiratory alkalosis results from hyperventilation causing

an excessive loss of carbon dioxide.• Metabolic alkalosis is caused by a great loss of hydrogen

ions or a gain in base perhaps from vomiting or use ofdrugs.

The Bohr effect

The Bohr effect

Learning outcome: To describe and explain the effects of raised

carbon dioxide concentrations on thehaemoglobin dissociation curve.

To learn how carbon dioxide is transported inblood.

What determines the loading andunloading of oxygen by haemoglobin?The amount of oxygen thathaemoglobin carries is affectedby:

1) The partial pressure of oxygenand

2) The partial pressure of carbondioxide

The presence of a high partial pressure of carbon dioxidecauses haemoglobin to release oxygen.

This is called the Bohr effect

HighpC02

Haemo-globinreleasesoxygen

The Bohr effect1. During respiration, CO2 is produced.

This diffuses into the blood plasmaand into the red blood cells.

2. Inside the red blood cells are manymolecules of an enzyme calledcarbonic anhydrase *.

3. It catalyses the reaction betweenCO2 and H2O.

Red cell

plasma

CO2 H2CO3

HCO3- + H+.CO2 + H2O H2CO3

carbondioxide

water carbonicacid

4. The resulting carbonic acid thendissociates into HCO3

- + H+.(Both reactions are reversible).

*H2O

HCO3-

The Bohr effect (continued)

5. Haemoglobin very readily combines withhydrogen ions forming haemoglobinic acid.

6. As a consequence haemoglobin releasessome of the oxygen it is carrying.

7. By removing hydrogen ions from thesolution, haemoglobin helps to maintain thepH of the blood close to neutral. It is actingas a buffer.

The Bohr effect

Three Oxygen Dissociationcurves illustrating the BohrEffect.

Increased carbon dioxide inthe blood causes a right-shiftin the curves, such that thehaemoglobin more easilyunloads the oxygen it iscarrying.

Oxygen Dissociation Curve

Curve B: Normalcurve

Curve A: Increasedaffinity for hgb, sooxygen keep close

Curve C: Decreasedaffinity for hgb, sooxygen released totissues

Bohr Effect

It all aboutoxygenaffinity!

Why is the Bohr effect useful?

High concentrations of carbon dioxide arefound in actively respiring tissues, whichneed oxygen. Due to the Bohr effect, thesehigh carbon dioxide concentrations causehaemoglobin to release its oxygen even morereadily than it would do otherwise.

How is carbon dioxide transported?

Carbon dioxide is mostly carried ashydrogencarbonate ions in bloodplasma, but also in combination withhaemoglobin in red blood cells(carbamino-haemoglobin) anddissolved as carbon dioxide moleculesin blood plasma.

Carbon dioxide transport

About 5% of the CO2produced simply dissolves inthe blood plasma.

Some CO2 diffuses into the redblood cells but instead of formingcarbonic acid, attaches directly ontothe haemoglobin molecules to formcarbaminohaemoglobin.

Since the CO2 doesn’t bind to thehaem groups the Haemoglobin isstill able to pick up O2.

About 85% of the CO2 produced byrespiration diffuses into the red blood cellsand forms carbonic acid under the controlof carbonic anhydrase.

The carbonic acid dissociates to producehydrogencarbonate ions (HCO3

-)

The HCO3- diffuses out of the red bloodcell into the plasma

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical

Chemistry: Techniques, principles, Correlations. Baltimore:Wolters Kluwer Lippincott Williams & Wilkins.

Carreiro-Lewandowski, E. (2008). Blood Gas Analysis andInterpretation. Denver, Colorado: Colorado Association forContinuing Medical Laboratory Education, Inc.

Sunheimer, R., & Graves, L. (2010). Clinical LaboratoryChemistry. Upper Saddle River: Pearson .

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